Production of TNF-α, nitric oxide and hydrogen peroxide by macrophages from mice with paracoccidioidomycosis that were fed a linseed oil-enriched diet

Omega-3 polyunsaturated fatty acids (n-3 PUFA) can modulate the immune system and their primary effect is on macrophage function. Paracoccidioidomycosis (PCM) is an endemic systemic mycosis in Latin America that is caused by the dimorphic fungus Paracoccidioides brasiliensis (Pb). Macrophages are the main defence against this pathogen and have microbicidal activity that is dependent on interferon-Γ and tumour necrosis factor (TNF)-α. These cytokines stimulate the synthesis of nitric oxide (NO) and hydrogen peroxide (H2O2), leading to the death of the fungus. To study the effect of n-3 PUFA on the host immune response during experimental PCM, macrophages that were obtained from animals infected with Pb18 and fed a diet enriched by linseed (LIN) oil were cultured and challenged with the fungus in vitro. The macrophage function was analysed based on the concentrations of TNF-α, NO and H2O2. LIN oil seems to influence the production of TNF-α during the development of disease. A diet enriched with LIN oil influences the microbicidal activity of the macrophages by inducing the production of cytokines and metabolites such as NO and H2O2, predominantly in the chronic phase of infection.

Antileishmanial activity of diterpene acids in copaiba oil

Leishmaniasis is a neglected tropical disease. According to the World Health Organization, there are approximately 1.5-two million new cases of cutaneous leishmaniasis each year worldwide. Chemotherapy against leishmaniasis is based on pentavalent antimonials, which were developed more than a century ago. The goals of this study were to investigate the antileishmanial activity of diterpene acids in copaiba oil, as well as some possible targets of their action against Leishmania amazonensis. Methyl copalate and agathic, hydroxycopalic, kaurenoic, pinifolic and polyaltic acids isolated from Copaifera officinales oleoresins were utilised. Ultrastructural changes and the specific organelle targets of diterpenes were investigated with electron microscopy and flow cytometry, respectively. All compounds had some level of activity against L. amazonensis. Hydroxycopalic acid and methyl copalate demonstrated the most activity against promastigotes and had 50% inhibitory concentration (IC50) values of 2.5 and 6.0 µg/mL, respectively. However, pinifolic and kaurenoic acid demonstrated the most activity against axenic amastigote and had IC50 values of 3.5 and 4.0 µg/mL, respectively. Agathic, kaurenoic and pinifolic acid caused significant increases in plasma membrane permeability and mitochondrial membrane depolarisation of the protozoan. In conclusion, copaiba oil and its diterpene acids should be explored for the development of new antileishmanial drugs.

Theory of mind and cognitive processes in aging and Alzheimer type dementia: a systematic review.

OBJECTIVES: Theory of mind (ToM) performance in aging and dementia of the Alzheimer type (DAT) has been a growing interest of researchers and recently, theoretical trends in ToM development have led to a focus on determining the cognitive skills involved in ToM performance. The aim of the present review is to answer three main questions: How is ToM assessed in aging and DAT? How does ToM performance evolve in aging and DAT? Do cognitive processes influence ToM performance in aging and DAT? METHOD: A systematic review was conducted to provide a targeted overview of recent studies relating ToM performance with cognitive processes in aging and DAT. RESULTS: RESULTS suggest a decrease in ToM performance, more pronounced in complex ToM tasks. Moreover, the review points up the strong involvement of executive functions, especially inhibition, and reasoning skills in ToM task achievement. CONCLUSION: Current data suggest that the structure of ToM tasks itself could lead to poor performance, especially in populations with reduced cognitive abilities.

No major impact of skin aging on the response of skin blood flow to a submaximal local thermal stimulus

La peau est sujette à un vieillissement intrinsèque (processus naturel et chronologique) et extrinsèque (processus induit par l'environnement et notamment les rayons UV). Plusieurs études ont montré que le vieillissement cutané s'accompagne d'une réduction de la densité capillaire au sein du derme et d'une dégradation de plusieurs protéines de la matrice extracellulaire. Cette atteinte morphologique est associée à une diminution de la capacité vasodilatatrice maximale de la microcirculation dermique et en particulier, de la réponse maximale du flux sanguin cutané à un échauffement local de la surface cutanée à des températures avoisinant les 43-44°C. Cette réponse, appelée hyperémie locale induite par la chaleur (local thermal hyperemia), est facilement mesurable par des investigations non invasives, telles que le laser Doppler. Nous avons entrepris cette étude afin d'investiguer les effets de l'âge sur la réactivité de la microcirculation dermique dans des zones cutanées exposées différemment aux rayons UV. Pour ce faire, nous avons étudié, chez des patients jeunes (18 à 30 ans, n=13) et des patients âgés (> 60 ans, n=13), la vasodilatation cutanée induite par réchauffement local de la peau, au niveau de 3 sites anatomiques différents (la cuisse, l'avant- bras et le front). Les mesures ont été effectuées au moyen d'un laser Doppler. Pour chaque sujet et chaque site, la température cutanée fut tout d'abord amenée à 34°C par 2 corps de chauffe (A et B), disposés de manière adjacente sur la peau. La température fut ensuite augmentée à 39°C (corps de chauffe A) et à 41°C (corps de chauffe B) pour une durée de 30 minutes, dans l'optique d'induire une vasodilatation sous- maximale. Ensuite, la température fut augmentée à 43 °C (corps de chauffe A et B) pour 15 minutes supplémentaires. Enfin, la vasodilatation maximale a été induite par un échauffement local à 44°C pour 15 minutes supplémentaires (corps de chauffe A et B). L'enregistrement séquentiel du flux sanguin cutané, effectué chaque minute par laser Doppler imager, donne des images sur lesquelles peut être calculé le flux sanguin cutané (unités de perfusion, PU). Par la suite, nous avons calculé les conductances vasculaires cutanées (CVC), en divisant le flux sanguin (PU) par la tension artérielle moyenne (mmHg), afin de permettre une normalisation entre les différents sujets. Les CVC, évaluées au temps de départ (température 34°C) et après vasodilatation maximale (température 44°C), étaient plus hautes au niveau du front qu'au niveau des 2 autres sites anatomiques. Sur les 3 sites, la CVC maximale (température 44°C) diminuait avec l'âge mais de façon moins importante au niveau du front, en comparaison avec les 2 autres sites. La réponse aux températures sous-maximales (température 39 et 41°C), exprimée en pourcentage de la CVC maximale, ne variait pas avec l'âge ni en fonction du site anatomique étudié. En conclusion, cette étude est la première à étudier simultanément l'hyperémie locale induite par la chaleur sur 3 sites ayant une exposition différente aux rayons UV. Le processus utilisé (laser Doppler imager) est également unique dans la littérature concernant les altérations de la microcirculation cutanée en lien avec l'âge. Cette étude confirme ainsi que le vieillissement cutané intrinsèque et/ou extrinsèque réduit la capacité vasodilatatrice maximale de la microcirculation dermique. Par contre, la réactivité à réchauffement local à des températures moindres ne semble pas être affectée.

Effectiveness of olive oil for the prevention of pressure ulcers caused in immobilized patients within the scope of primary health care: study protocol for a randomized controlled trial.

BACKGROUND Pressure ulcers are considered an important issue, mainly affecting immobilized older patients. These pressure ulcers increase the care burden for the professional health service staff as well as pharmaceutical expenditure. There are a number of studies on the effectiveness of different products used for the prevention of pressure ulcers; however, most of these studies were carried out at a hospital level, basically using hyperoxygenated fatty acids (HOFA). There are no studies focused specifically on the use of olive-oil-based products and therefore this research is intended to find the most cost-effective treatment and achieve an alternative treatment. METHODS/DESIGN The main objective is to assess the effectiveness of olive oil, comparing it with HOFA, to treat immobilized patients at home who are at risk of pressure ulcers. As a secondary objective, the cost-effectiveness balance of this new application with regard to the HOFA will be assessed. The study is designed as a noninferiority, triple-blinded, parallel, multi-center, randomized clinical trial. The scope of the study is the population attending primary health centers in Andalucía (Spain) in the regional areas of Malaga, Granada, Seville, and Cadiz. Immobilized patients at risk of pressure ulcers will be targeted. The target group will be treated by application of an olive-oil-based formula whereas the control group will be treated by application of HOFA to the control group. The follow-up period will be 16 weeks. The main variable will be the presence of pressure ulcers in the patient. Secondary variables include sociodemographic and clinical information, caregiver information, and whether technical support exists. Statistical analysis will include the Kolmogorov-Smirnov test, symmetry and kurtosis analysis, bivariate analysis using the Student's t and chi-squared tests as well as the Wilcoxon and the Man-Whitney U tests, ANOVA and multivariate logistic regression analysis. DISCUSSION The regular use of olive-oil-based formulas should be effective in preventing pressure ulcers in immobilized patients, thus leading to a more cost-effective product and an alternative treatment. TRIAL REGISTRATION Clinicaltrials.gov identifier: NCT01595347.

A Comparative analysis of oil production setors in Saudi Arabia and the United Arab Emirates

Aquest article s'aplica un enfocament comparatiu de la gestió del sector petrolier en dos països rics en petroli a l'Orient Mitjà: Aràbia Saudita i els Emirats Àrabs Units (EAU). Més explícitament, s'examinen els factors que millor expliquen la variació en les estratègies que han vingut aplicant en el sector des de l'establiment de les seves empreses petrolieres nacionals (NOC). Recorrent a la literatura sobre expropiació / privatització en el camp d'Estudis de l'Energia, en aquest treball es proposa un marc teòric per analitzar la lògica que hi ha al darrera de les diferents formes d'exploració i les estratègies de producció en el sector petrolier. Teòricament, aquesta investigació té com a objectiu avançar en un conjunt d'eines d'anàlisi per abordar millor i entendre els determinants reals del procés de presa de decisions en el upstream. Empíricament, el model es prova en els casos divergents d'Aràbia Saudita i els Emirats Àrabs Units, i una sèrie de lliçons s'han extret. En última instància, aquest treball ha d'augmentar la conscienciació entre els erudits i els polític, tant sobre el poc coneixement que tenim sobre els mecanismes interns que impulsen les estratègies ascendents en el majors estats productor de petroli.

Antileishmanial activity of the essential oil from Tetradenia riparia obtained in different seasons

The herbaceous shrub Tetradenia riparia has been traditionally used to treat inflammatory and infectious diseases. Recently, a study showed that T. riparia essential oil (TrEO) obtained in summer has antileishmanial effects, although these results could be influenced by seasonal variation. This study evaluated the activity of the TrEO obtained in different seasons against Leishmania (Leishmania) amazonensis, in vitro and in vivo. The compounds in the TrEO were analysed by gas chromatography-mass spectrometry; terpenoids were present and oxygenated sesquiterpenes were the majority compounds (55.28%). The cytotoxicity and nitric oxide (NO) production were also tested after TrEO treatment. The TrEO from all seasons showed a 50% growth inhibitory concentration for promastigotes of about 15 ng/mL; at 30 ng/mL and 3 ng/mL, the TrEO reduced intracellular amastigote infection, independently of season. The TrEO from plants harvested in summer had the highest 50% cytotoxic concentration, 1,476 ng/mL for J774.A1 macrophages, and in spring (90.94 ng/mL) for murine macrophages. NO production did not change in samples of the TrEO from different seasons. The antileishmanial effect in vivo consisted of a reduction of the parasite load in the spleen. These results suggest that the TrEO has potential effects on L. (L.) amazonensis, consonant with its traditional use to treat parasitic diseases.

Light-induced retinal degeneration correlates with changes in iron metabolism gene expression, ferritin level, and aging.

PURPOSE: Retinal degeneration is associated with iron accumulation in several rodent models in which iron-regulating proteins are impaired. Oxidative stress is catalyzed by unbound iron. METHODS: The role of the heavy chain of ferritin, which sequesters iron, in regulating the thickness of the photoreceptor nuclear layer in the 4- and 16-month-old wild-type H ferritin (HFt(+/+)) and heterozygous H ferritin (HFt(+/-)) mice was investigated, before and 12 days after exposure to 13,000-lux light for 24 hours. The regulation of gene expression of the various proteins involved in iron homeostasis, such as transferrin, transferrin receptor, hephaestin, ferroportin, iron regulatory proteins 1 and 2, hepcidin, ceruloplasmin, and heme-oxygenase 1, was analyzed by quantitative (q)RT-PCR during exposure (2, 12, and 24 hours) and 24 hours after 1 day of exposure in the 4-month-old HFt(+/+) and HFt(+/-) mouse retinas. RESULTS: Retinal degeneration in the 4-month-old HFt(+/-) mice was more extensive than in the HFt(+/+) mice. Yet, it was more extensive in both of the 16-month-old mouse groups, revealing the combined effect of age and excessive light. Injury caused by excessive light modified the temporal gene expression of iron-regulating proteins similarly in the HFt(+/-) and HFt(+/+) mice. CONCLUSIONS: Loss of one allele of H ferritin appears to increase light-induced degeneration. This study highlighted that oxidative stress related to light-induced injury is associated with major changes in gene expression of iron metabolism proteins.

Epiphyseal fracture of distal humerus in children, treated with bio-absorbable materials: one year follow-up

Introduction: The use of bioabsorbable materials for orthopaedic useand traumatic fracture fixation in children has been poorly investigatedin the litterature and the effects on growing bones seem contradictory.The aim of the study is to compare the clinical and radiological resultsand evolution between bioabsorbable and traditional K-Wires for thetreatment of elbow epiphyseal fractures in children.Method: From jan. 2008 to Dec. 2009 21 children with similar fracturesand age were separated in two groups according to the way of fracturefixation: bioabsorbable K-Wire group and traditional K-Wire group.Follow-up was done at 3, 6 and 12 month post-operatively. Range ofmotion and elbow stability were measured for all patients. Theradiological evolution of the two groups were compared in term ofconsolidation, ossous resorption and radiolucencies. The clinicalresults were compared according to the Mayo Elbow Peformancescore. Controlateral elbow is compared with injured elbow in the twogroups.Results: In the bioabsorbable K-wire group, there were 10 children,including 5 girles and 5 boys with an average age of 9.5 years, rangingfrom 5 to 14 years. They were 7 external condylar fractures and3 epitrochlear fractures. In the traditional K-Wire group there were11 children, 2 girls and 9 boys with an average age of 7.6 years,ranging from 4 to 14 years. There were 10 external condylar fracturesand 1 epitrochlear fracture. At first follow up. The Mayo ElbowPerformance score was 93.8 (85-100 )for the bioabsorbable K-Wiregroup and 95.5 (85-100) for the traditional K-Wire group. In twochildren from the bioabsorbable K-Wire group there were transitoryradiolucencies along the wire tract on the x-ray, without clinicalmanifestation of it.We didn't see any premature closure of growingcartilage.Discussion: There is no significant differencies in term of clinical andradiological outcome between the two groups. The use ofbioabsorbable pins seems to be a good alternative to removabletraditional materials, avoiding a second operation.

Adult hippocampal neurogenesis inversely correlates with microglia in conditions of voluntary running and aging.

Adult hippocampal neurogenesis results in the formation of new neurons and is a process of brain plasticity involved in learning and memory. The proliferation of adult neural stem or progenitor cells is regulated by several extrinsic factors such as experience, disease or aging and intrinsic factors originating from the neurogenic niche. Microglia is very abundant in the dentate gyrus (DG) and increasing evidence indicates that these cells mediate the inflammation-induced reduction in neurogenesis. However, the role of microglia in neurogenesis in physiological conditions remains poorly understood. In this study, we monitored microglia and the proliferation of adult hippocampal stem/progenitor cells in physiological conditions known to increase or decrease adult neurogenesis, voluntary running and aging respectively. We found that the number of microglia in the DG was strongly inversely correlated with the number of stem/progenitor cells and cell proliferation in the granule cell layer. Accordingly, co-cultures of decreasing neural progenitor/glia ratio showed that microglia but not astroglia reduced the number of progenitor cells. Together, these results suggest that microglia inhibits the proliferation of neural stem/progenitor cells despite the absence of inflammatory stimulus.

Fish oil after abdominal aorta aneurysm surgery

OBJECTIVE: Fish oil (FO) may attenuate the inflammatory response after major surgery such as abdominal aortic aneurysm (AAA) surgery. We aimed at evaluating the clinical impact and safety aspects of a FO containing parenteral nutrition (PN) after AAA surgery. METHODS: Intervention consisted in 4 days of either standard (STD: Lipofundin medium-chain triglyceride (MCT): long-chain triglyceride (LCT)50%-MCT50%) or FO containing PN (FO: Lipoplus: LCT40%-MCT50%-FO10%). Energy target were set at 1.3 times the preoperative resting energy expenditure by indirect calorimetry. Blood sampling on days 0, 2, 3 and 4. Glucose turnover by the (2)H(2)-glucose method. Muscle microdialysis. Clinical data: maximal daily T degrees, intensive care unit (ICU) and hospital stay. RESULTS: Both solutions were clinically well tolerated, without any differences in laboratory safety parameters, inflammatory, metabolic data, or in organ failures. Plasma tocopherol increased similarly; with FO, docosahexaenoic and eicosapentaenoic acid increased significantly by day 4 versus baseline or STD. To increased postoperatively, with a trend to lower values in FO group (P=0.09). After FO, a trend toward shorter ICU stay (1.6+/-0.4 versus 2.3+/-0.4), and hospital stay (9.9+/-2.4 versus 11.3+/-2.7 days: P=0.19) was observed. CONCLUSIONS: Both lipid emulsions were well tolerated. FO-PN enhanced the plasma n-3 polyunsaturated fatty acid content, and was associated with trends to lower body temperature and shorter length of stay.